| The goal of this dissertation is to understand the immune responses generated against cutaneous herpes simplex virus (HSV) infection, with an emphasis on the role of gamma-interferon (IFN-;A T-cell mediated inflammatory response dominated by IFN-;To test the principle that genetically engineered epitopes in a plasmid DNA can efficiently induce specific immunity, a study on HSV-specific immune responses induced by vaccinating mice with a plasmid DNA (pcMini) encoding cytotoxic T lymphocyte (CTL), helper T and B cell epitopes from HSV is described in this dissertation. Following immunizations with pcMini, mice developed epitope-specific CTLs comparable to the responses induced by live HSV. Antibody, lymphoproliferative responses, and T cell cytokine release were also detected. The protection provided by minigene vaccination was significant; however, not as efficient as live virus immunization. The DNA minigene approach may prove useful to define and induce immune responses against minimal antigenic determinants.;To address the question of whether immune responses to a vector-encoded antigen can be enhanced by the activation of antigen-presenting cells in the local environment, the effects of co-inoculation of an HSV glycoprotein (gB)-expressing plasmid with a plasmid encoding mouse granulocyte-macrophage colony-stimulatory factor (GM-CSF) on modulation of gB-specific immune responses are evaluated in this dissertation. The results show that co-administration of GM-CSF DNA provided increased resistance to HSV infection and this protective response could be related to the enhanced immune induction of CD4+ T cells and B cells responses. |
